Beta adrenergic recptor agonists constitute important therapy in the treatment of several allergic diseases, including bronchial asthma. In this proposal, it is argued that there exist at least two subtypes of beta receptors which are responsible for inhibiting histamine release from lung. Supporting preliminary data is also presented which suggests that these two subtypes act by different mechanisms, one cyclic AMP-dependent and the other cyclic AMP-independent. Pharmacological studies will extend observations on release from the lung by studying the effect of selective beta antagonists. An important part of this application is the proposal to isolate mast cells from the guinea-pig lung by affinity chromatography. With isolated and purified lung mast cells, the actions of the beta agonists can more confidently by confined to the cell itself. Studies on isolated mast cells will consist of quantitating the effects of the selective beta agonists for their abilities to inhibit noncytolytic histamine release evoked by several immunologic and nonimmunologic stimuli. The dependence on extracellular calcium and phosphatidylserine for release by each of these stimuli will be examined in order to determine the degree to which they rely on the cell membrane calcium gate mechanism. Relative potencies and apparent KA values for the beta agonists will be determined for their abilities to inhibit release by the several stimuli. Also, PA2 and KB values for beta antagonists will be determined as another criterion to subclassify the beta receptors which modulate histamine release from the mast cells. It is speculated that one of the beta receptors on mast cells controls the calcium gate and the other controls intracellular events in the release mechanism. It is further proposed to examine the beta agonists and antagonists for changes in cyclic AMP levels in the isolated mast cells. Using relative potencies and apparent dissociation constants, we expect to associate one of the receptors with cyclase activation.